N-methyl-D-aspartate receptor-mediated, calcium-induced calcium release in rat dentate gyrus/CA4 in vivo.
Previously, by using in vivo microdialysis, we demonstrated a huge release of 45Ca2+ from prelabeled tissues to dialysate that was evoked by application of N-methyl-D-aspartate (NMDA) to the rat dentate gyrus (DG) and sector 4 of the cornu ammonis. To establish the mechanism of this phenomenon, in the present study, we characterized its NMDA receptor dependence, investigated the mechanism of 45Ca2+ removal from the cells, and evaluated the possible involvement of calcium-binding protein calbindin D28k and of ryanodine receptors. Microdialysis experiments demonstrated a dose-response relation between NMDA and 45Ca2+ release and sensitivity of this phenomenon to inhibition by 10 microM MK-801 and 5 mM 5-(N,N-dimethyl)-amiloride, thus indicating the NMDA receptor dependence and a role of Na+/Ca2+ exchanger in mediating 45Ca2+ release from cells. Immunocytochemical experiments confirmed that DG granule cells in the investigated inbred rat strain are strongly calbindin D28k-immunopositive, indicating probable involvement of this protein. However, microdialysis studies demonstrated that NMDA-evoked 45Ca2+ release was suppressed by 100 microM dantrolene and 250 microM ryanodine, whereas 50 microM ryanodine stimulated this effect. This points to a key role in the investigated phenomenon of calcium-induced calcium release (CICR) via ryanodine receptors. To our knowledge, this is the first in vivo demonstration of NMDA-evoked CICR. We postulate the usefulness of microdialysis in such studies.
Lazarewicz
J W
JW
Department of Neurochemistry, Medical Research Centre, Polish Academy of Sciences, Warsaw. neurochemia@ibbrain.ibb.waw.pl
Rybkowski
W
W
Sadowski
M
M
Ziembowicz
A
A
Alaraj
M
M
Wegiel
J
J
Wisniewski
H M
HM
D000818:Animals; D064092:Calbindin 1; D064026:Calbindins; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D002132:Calcium Radioisotopes; D018891:Dentate Gyrus / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology; D064030:S100 Calcium Binding Protein G / Q000502:physiology; D019831:Sodium-Calcium Exchanger / Q000502:physiology
C576500:Calb1 protein, rat; D064092:Calbindin 1; D064026:Calbindins; D002132:Calcium Radioisotopes; D016194:Receptors, N-Methyl-D-Aspartate; D019837:Ryanodine Receptor Calcium Release Channel; D064030:S100 Calcium Binding Protein G; D019831:Sodium-Calcium Exchanger; D002118:Calcium